8DTB

Focus/local refined map in C1 of signal subtracted RyR1 particles in complex with ImperaCalcin

Summary for 8DTB

• Entry DOI: 10.2210/pdb8dtb/pdb
• EMDB information: 27680 27695
• Descriptor: Imperacalcin, Ryanodine receptor 1, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: ryanodine receptor, ion channel, snake toxin, calcin, complex, membrane protein, toxin
• Biological source: Oryctolagus cuniculus (rabbit); More
• Total number of polymer chains: 5
• Total formula weight: 2270022.29

Authors

Haji-Ghassemi, O.,Van Petegm, F. (deposition date: 2022-07-25, release date: 2023-05-31, Last modification date: 2024-03-13)

Primary citation

Haji-Ghassemi, O.,Chen, Y.S.,Woll, K.,Gurrola, G.B.,Valdivia, C.R.,Cai, W.,Li, S.,Valdivia, H.H.,Van Petegem, F.
Cryo-EM analysis of scorpion toxin binding to Ryanodine Receptors reveals subconductance that is abolished by PKA phosphorylation.
Sci Adv, 9:eadf4936-eadf4936, 2023

PubMed Abstract: Calcins are peptides from scorpion venom with the unique ability to cross cell membranes, gaining access to intracellular targets. Ryanodine Receptors (RyR) are intracellular ion channels that control release of Ca from the endoplasmic and sarcoplasmic reticulum. Calcins target RyRs and induce long-lived subconductance states, whereby single-channel currents are decreased. We used cryo-electron microscopy to reveal the binding and structural effects of imperacalcin, showing that it opens the channel pore and causes large asymmetry throughout the cytosolic assembly of the tetrameric RyR. This also creates multiple extended ion conduction pathways beyond the transmembrane region, resulting in subconductance. Phosphorylation of imperacalcin by protein kinase A prevents its binding to RyR through direct steric hindrance, showing how posttranslational modifications made by the host organism can determine the fate of a natural toxin. The structure provides a direct template for developing calcin analogs that result in full channel block, with potential to treat RyR-related disorders.

PubMed: 37224245
DOI: 10.1126/sciadv.adf4936

Experimental method

ELECTRON MICROSCOPY (3.14 Å)